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Copyright ©The Author(s) 2020.
World J Gastroenterol. Mar 21, 2020; 26(11): 1128-1141
Published online Mar 21, 2020. doi: 10.3748/wjg.v26.i11.1128
Table 1 Pathological classification of most common pancreatic cysts
Inflammatory fluid collections
Acute peripancreatic fluid collections
Pseudocysts
Acute necrotic collections
Walled-off pancreatic necrosis
Non-neoplastic
True cysts
Mucinous non-neoplastic cysts
Lymphoepithelial cysts
Pancreatic cystic neoplasms
Serous cystic neoplasms
Mucinous cystic neoplasm
Intrapapillary mucinous neoplasm
Solid papillary neoplasm
Table 2 Surveillance of pancreatic cysts
Surveillance of pancreatic cysts
European guidelines[28]Mucinous cystic neoplasm: Cyst size < 4 cm without symptoms or mural nodules should undergo surveillance every 6 mo for the 1st year using EUS/MRI or both[29]. Followed by annually, if no changes. Lifelong surveillance if they are fit for surgery
Intraductal papillary mucinous neoplasm (IPMN): Every 6 mo for cysts less than 4cm or low-grade dysplasia for the 1st year with CA 19-9, EUS/MRI or both. Followed by yearly, until no longer fit for surgery
After surgical resection, HGD or MD-IPMN should have imaging every 6 mo for the 1st 2 yr. Followed by yearly surveillance. Lifelong surveillance if they are fit for surgery
American College of Gastroenterology (ACG) guidelines[30]Intraductal papillary mucinous neoplasm/Mucinous cystic neoplasm (IPMN/MCN): Cyst size < 1 cm: MRI every 2 yr × 4 yr. If stable in size, consider prolonging the time interval. Any increase in size, consider EUS-FNA in 6 mo and reevaluate
Cyst size 1-2 cm: MRI every 1 yr × 3 yr. If stable, consider MRI every 2 yr × 4 yr. Once stable, consider prolonging the interval
Cyst size 2-3 cm: MRI/EUS every 6-12 mo for 3 yr. If stable, MRI every 1-year × 4 yr. Once stable, consider prolonging the interval. Any increase in cyst size should be referred to the multidisciplinary group and consider EUS-FNA
Cyst size > 3 cm: Referral to the multidisciplinary team. MRI alternating with EUS every 6 mo for 3 yr. Once stable in size, MRI alternating with EUS every year for 4 yr. Once stable in size, consider prolonging the interval
Stop surveillance when a patient is no longer a surgical candidate or after surgical resection of MCN if no invasive cancer
The risk of recurrence of IPMN after surgery varies based on the degree of dysplasia
EUS/MRI every 6 mo after surgical resection of IPMN with HGD
MRI every 2 yr after surgical resection of IPMN with low to intermediate grade dysplasia in the absence of pancreatic cysts in the remnant pancreas. However, if IPMN or pancreatic cysts are present in the remnant pancreas, then surveillance should be based on cyst size
American Gastroenterology Association (AGA) guidelines[31]Cyst size < 3 cm without a solid component or PD dilation recommend MRI in 1 yr, followed by every 2 yr for 5 yr.
Recommend stopping surveillance if no change in cyst characteristics after 5 yr or not a surgical candidate
Revised IAP 2017 or revised Fukuoka guidelines[32]Branch duct-Intraductal papillary mucinous neoplasm (BD-IPMN): Cysts without high-risk stigmata should undergo CT/MRI every 3-6 mo to establish stability if prior imaging is not available. Subsequently, surveillance should be based on size stratification
For cyst size < 1 cm, CT/MRI every 2 yr
For cyst size 1-2 cm, CT/MRI every 6 mo for a year, followed by every year for 2 yr and prolong the interval if stable
For cyst size 2-3 cm, EUS in 3-6 mo for 1 year. Increase the interval to 1 yr with EUS/MRI as appropriate. Consider surgery in young patients with a need for prolonged surveillance
For cyst size > 3 cm, close surveillance alternating MRI with EUS every 3-6 mo. Strongly recommend surgery in young patients
In surgically resected IPMN, surveillance is recommended with cross-sectional imaging twice a year for patients with a family history of pancreatic ductal adenocarcinoma, surgical margin positive for HGD and non-intestinal sub-type of IPMN. For all others, every 6-12 mo of cross-sectional imaging is recommended
American College of Radiology (ACR) guidelines[33]Cyst size < 1.5 cm and age < 65 yr: CT/MRI every year for 5 yr, followed by every 2 yr for 4 yr. Stop surveillance if stable over 9 yr
Cyst size < 1.5 cm and age 65-79 yr: CT/MRI every 2 yr for a total of 10 yr. Stop surveillance if the cyst is stable for 10 yr
If there is interval change and cyst size < 1.5 cm, consider CT/MRI every year or EUS-FNA. EUS-FNA shows a mucinous cyst or indeterminate cyst, CT/MRI every 6 mo for 2 yr, followed by every year for 2 yr and every 2 yr for 6 yr. Stop surveillance if the cyst is stable after 10 yr
Any further interval growth of cyst should be referred to surgery for further evaluation
Cyst size 1.5-1.9 cm with MPD communication: CT/MRI every year for 5 yr, followed by every 2 yr for 4 yr. Stop surveillance if cyst size stable for over 9 yr
Cyst size 2-2.5 cm with MPD communication: CT/MRI every 6 mo for 2 yr, followed by every year for 2 yr and subsequently every 2 yr for 6 yr. Stop surveillance if cyst size is stable for 10 yr
If there is interval change and cyst size ≤ 2.5 cm, CT/MRI every 6 mo for 2 yr, followed by every year for 2 yr and subsequently every 2 yr. If cyst size > 2.5 cm, consider EUS-FNA
If EUS-FNA shows a mucinous cyst or indeterminate cyst, CT/MRI every 6 mo for 2 yr, followed by every year for 2 yr and every 2 yr for 6 yr
EUS-FNA is recommended for any mural nodule, wall thickening, dilation of MPD ≥ 7 mm or extrahepatic biliary obstruction/Jaundice irrespective of cyst size
Cyst size 1.5-2.5 cm without MPD communication or cannot be determined: CT or MRI every 6 mo for 2 yr, followed by every year for 2 yr and subsequently every 2 yr for 6 yr. Stop surveillance if cyst size is stable after 10 yr
If there is interval change and cyst size < 2.5 cm, consider CT/MRI every 6 mo for 1 year, followed by every year for 5 yr and subsequently every 2 yr. If cyst size is > 2.5 cm, consider EUS-FNA
Cyst size >2.5 cm: If a cyst is a low risk by imaging, consider CT/MRI every 6 mo for 2 yr. If stable after 2 yr, CT/MRI every yr for 2 yr and subsequently every 2 yr for 6 yr. Stop surveillance if stable in cyst size
Any interval changes in cyst size, consider EUS-FNA. Any high-risk stigmata like jaundice, enhancing mural nodule, wall thickening and MPD ≥ 10 mm refer to surgery for evaluation
Age ≥ 80 yr with cyst size ≤ 2.5 cm: CT/MRI every 2 yr for 4 yr. Stop surveillance if cyst size is stable in size: If there is interval change and cyst size ≤ 2.5 cm, consider CT/MRI every year. Stop surveillance if the cyst stabilizes or not a surgical candidate; If there is interval change and cyst size > 2.5 cm, consider EUS-FNA
Age ≥ 80 yer with cyst size ≥ 2.5 cm: If low risk by imaging, consider CT/MRI every 2 yr for 4 yr. Stop surveillance if cyst size is stable; If there is interval change in cyst size, consider EUS-FNA
High risk (mural nodule, wall thickening, dilation of MPD ≥ 7 mm or extrahepatic biliary obstruction/Jaundice) features by imaging should be referred to EUS-FNA
High-risk stigmata (jaundice, enhancing mural nodule, wall thickening, and MPD ≥ 10 mm) by EUS or imaging refer to surgery for evaluation
Table 3 Cyst fluid analysis
Cyst fluid analysis
European guidelines[28]Cyst fluid CEA with cytology, or KRAS/GNAS mutation analysis for differentiating IPMN or MCN from other pancreatic cysts
American College of Gastroenterology (ACG) guidelines[30]Cyst fluid CEA to differentiate IPMNs and MCNs from other cyst types
Cyst fluid cytology to assess for HGD or pancreatic cancer when imaging features are alone insufficient for surgery
Molecular markers like KRAS or GNAS mutations can help identify IPMNs or MCNs when the diagnosis is not clear
American Gastroenterology Association (AGA) guidelines[31]Cyst fluid cytology is recommended for the evaluation of high-risk features on imaging. The role of molecular markers is not clear and further research is needed
Revised IAP 2017 guidelines[32]Cyst fluid CEA can distinguish mucinous from non-mucinous cysts. CEA level ≥ 192-200 ng/mL is 80% accurate for the diagnosis of mucinous cyst[38,45]
Cyst fluid cytology can be diagnostic but sometimes limited by scant cellularity[43,44]
Cyst fluid amylase can differentiate benign from malignant MCN and amylase levels are higher in pseudocysts than non-pseudocysts[45]. The role of molecular markers like KRAS and GNAS mutations is still evolving
American College of Radiology guidelines[33]Cyst fluid CEA ≥ 192 ng/mL can help identify a mucinous cyst[46]
Cyst fluid amylase > 250 IU/L suggests pseudocyst[11]
KRAS and GNAS molecular markers can help differentiate mucinous from non-mucinous cysts[47]
Cyst cytology can identify dysplastic cells
Table 4 Endoscopic ultrasound-fine needle aspiration indications
Endoscopic ultrasound-Fine needle aspiration indications
European guidelines[28]Differentiating mucinous vs non-mucinous
Malignant vs benign
CT or MRI unclear
Only when results are expected to change clinical management
American College of Gastroenterology guidelines[30]Jaundice
Acute pancreatitis
Significantly elevated serum CA 19-9
Mural nodule
A solid component within cyst or pancreatic parenchyma
Dilation of MPD ≥ 5 mm
Focal dilation of PD
Cyst size > 3 cm
When the diagnosis of cysts is unclear or results will likely alter management
Cyst fluid CEA to differentiate IPMNs and MCNs from other cyst types
New onset or worsening diabetes
Increase in cyst size > 3 mm/yr
American Gastroenterology Association guidelines[31]At least 2 high-risk features
Cyst size ≥ 3 cm
Dilated MPD
Solid component
Revised IAP 2017 or revised Fukuoka guidelines[32]Pancreatitis
Cyst ≥ 3 cm
Enhancing mural nodule < 5 mm
Thickened/enhancing cyst wall
Main duct size 5-9 mm
An abrupt change in caliber of the pancreatic duct with distal pancreatic atrophy
Lymphadenopathy
Increased serum level of CA19-9
Cyst growth rate ≥ 5 mm/2 yr
American College of Radiology guidelines[33]Mural nodule
Wall thickening
Dilation of MPD ≥ 7 mm
Extrahepatic biliary obstruction/Jaundice
Table 5 Indications of surgery for pancreatic cysts
Absolute indications of surgeryRelative indications of surgery
European guidelines[28]Intraductal papillary mucinous neoplasm: Cytology positive for malignancy/High-grade dysplasia; Solid mass; Jaundice; Mural nodule ≥ 5 mm; Main pancreatic duct dilation > 10 mmCyst growth rate > 5 mm/yr
Mucinous cystic neoplasm: Size ≥ 4 cmSerum CA 19-9 > 37 U/mL
Symptomatic Mural noduleMPD dilation 5-9 mm
Cyst diameter ≥ 40 mm
New-onset diabetes mellitus
Acute pancreatitis related to IPMN
Mural nodule < 5 mm
American College of Gastroenterology guidelines[30]Intraductal papillary mucinous neoplasm or Mucinous cystic neoplasm:N/A
Referral to EUS-FNA/Multidisciplinary; team:
Jaundice
Acute pancreatitis
Significantly elevated CA 19-9
Mural nodule
A solid component in cyst/pancreatic parenchyma
MPD > 5 mm
Focal dilation of PD or MD-IPMN
HGD/Pancreatic cancer on cytology
American Gastroenterology Association guidelines[31]Pancreatic cysts:N/A
EUS-FNA cytology positive for -
HGD/cancer
Both solid component and dilated PD on MRI and EUS
Revised IAP 2017 or revised Fukuoka guidelines[32]Obstructive jaundice with pancreatic head cystPancreatitis
Enhancing mural nodule ≥ 5 mmEnhancing mural nodule < 5 mm
MPD ≥ 10 mmThickened/enhancing cyst wall
Main duct size 5-9 mm
An abrupt change in caliber of the pancreatic duct with distal pancreatic atrophy
Lymphadenopathy
Increase in serum level of CA 19-9
Cyst growth rate ≥ 5 mm/2 yr
American College of Radiology guideline[33]Obstructive jaundice with a cyst in the head of the pancreasCyst ≥ 3 cm
Enhancing solid component within a cystThickened/enhancing cyst wall
MPD > 10 mm in the absence of obstructionNon-enhancing mural nodule
MPD ≥ 7 mm